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Nardelli, B. et al.

Nardelli, Zaritskaya, Semenuk, Cho, LaFleur, Shah, Ullrich, Girolomoni, Albanesi, Moore,

Regulatory effect of IFN-kappa, a novel type I IFN, on cytokine production by cells of the innate immune system.

IFN-kappa is a recently identified type I IFN that exhibits both structural and functional homology with the other type I IFN subclasses. In this study, we have investigated the effect of IFN-kappa on cells of the innate immune system by comparing cytokine release following treatment of human cells with either IFN-kappa or two recombinant IFN subtypes, IFN-beta and IFN-alpha2a. Although IFN-alpha2a failed to stimulate monocyte cytokine secretion, IFN-kappa, like IFN-beta, induced the release of several cytokines from both monocytes and dendritic cells, without the requirement of a costimulatory signal. IFN-kappa was particularly effective in inhibiting inducible IL-12 release from monocytes. Unlike IFN-beta, IFN-kappa did not induce release of IFN-gamma by PBL. Expression of the IFN-kappa mRNA was observed in resting dendritic cells and monocytes, and it was up-regulated by IFN-gamma stimulation in monocytes, while IFN-beta mRNA was minimally detectable under the same conditions. Monocyte and dendritic cell expression of IFN-kappa was also confirmed in vivo in chronic lesions of psoriasis vulgaris and atopic dermatitis. Finally, biosensor-based binding kinetic analysis revealed that IFN-kappa, like IFN-beta, binds strongly to heparin (K(d): 2.1 nM), suggesting that the cytokine can be retained close to the local site of production. The pattern of cytokines induced by IFN-kappa in monocytes, coupled with the unique induction of IFN-kappa mRNA by IFN-gamma, indicates a potential role for IFN-kappa in the regulation of immune cell functions.[1]

References

Regulatory effect of IFN-kappa, a novel type I IFN, on cytokine production by cells of the innate immune system. Nardelli, B., Zaritskaya, L., Semenuk, M., Cho, Y.H., LaFleur, D.W., Shah, D., Ullrich, S., Girolomoni, G., Albanesi, C., Moore, P.A. J. Immunol. (2002) [Pubmed]

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